Attenuation of high-frequency (30-200 Hz) thalamocortical EEG rhythms as correlate of anaesthetic action: evidence from dexmedetomidine.

Background: Gamma (30-80 Hz) and high-gamma (80-200 Hz) thalamocortical EEG rhythms are involved in conscious processes and are attenuated by isoflurane and propofol. To explore the hypothesis that this attenuation is a correlate of anaesthetic action, we characterized the effect dexmedetomidine, a selective adrenergic α-2 agonist with lesser hypnotic potency, on these rhythms. Methods: We recorded local field potentials from barrel cortex and ventroposteromedial thalamic nucleus in ten previously instrumented rats to measure spectral power (30-50 Hz, 51-75 Hz, 76-125 Hz, 126-200 Hz bands) during baseline, at four dexmedetomidine plasma concentrations obtained by i.v. target-controlled infusion (1.86, 3.75, 5.63 and 7.50 ng ml -1 ), and during recovery. Thalamocortical coherence over 0.3-200 Hz was also measured. Results: Loss of righting reflex (LORR) occurred with 5.63 ng ml -1 . Dexmedetomidine produced a linear concentration-dependent attenuation of cortical ( P <0.04) and thalamic ( P ≤ 0.0051) log power in all bands. Slopes for cortex and thalamus were similar. The slope for dexmedetomidine on thalamic power in the 76-200 Hz range was less than half that of the other agents ( P <0.003). LORR was associated with an increase in delta band (0.3-4.0 Hz) thalamocortical coherence ( P <0.001). Increased low-frequency coherence also occurred with propofol and isoflurane. Conclusions: Dexmedetomidine attenuates high-frequency thalamocortical rhythms, but to a lesser degree than isoflurane and propofol. The main differences between dexmedetomidine and the other anaesthetics involved thalamic rhythms, further substantiating the link between impaired thalamic function and anaesthesia. Increased delta coherence likely reflects cyclic hyperpolarization of thalamocortical networks and may be a marker for loss of consciousness.

Current issues in the identification and treatment of metabolically healthy but obese individuals.

A unique subset of obese individuals who appear to be protected from the development of metabolic disturbances has been identified in the medical literature and is termed metabolically healthy but obese (MHO). Part of the issue is that there are no clear accepted criteria on the definition of MHO and the biological mechanisms to explain this phenotype are still unknown which render findings and/or conclusions difficult to interpret and making the application of this concept difficult in clinical practice. With the current definitions, the true prevalence of the MHO phenotype in the general population varies widely from approximately 3-57% of obese adults. In several prospective studies, the MHO individual has been associated with a similar risk of developing type 2 diabetes, cardiovascular disease and mortality when compared to healthy normal weight subjects; however, there is evidence to refute this concept. Furthermore, the current evidence cannot confirm that MHO subjects are permanently protected from the risk of developing metabolic disturbances associated with obesity. Currently, no standard practice guidelines for the treatment of MHO can be proposed, however, a regular surveillance of the waist circumference and cardio-metabolic risk factors such as elevated triglycerides, glycaemia, HOMA, C-reactive protein and low HDL, as well as the prevention of any further weight gain seem to represent the most prudent and sound attitude in the management of MHO subjects.

Partial antagonism of propofol anaesthesia by physostigmine in rats is associated with potentiation of fast (80-200 Hz) oscillations in the thalamus.

BACKGROUND: Positron emission tomography studies in human subjects show that propofol-induced unconsciousness in humans is associated with a reduction in thalamic blood flow, suggesting that anaesthesia is associated with impairment of thalamic function. A recent study showed that antagonism of propofol-induced unconsciousness by the anticholinesterase physostigmine is associated with a marked increase in thalamic blood flow, supporting the implication of the thalamus. The aim of the present study was to assess the role of the thalamus in the antagonistic effects of physostigmine during propofol anaesthesia using electrophysiological recordings in a rat model. METHODS: Local field potentials were recorded from the barrel cortex and ventroposteromedial thalamic nucleus in 10 chronically instrumented rats to measure spectral power in the gamma/high-gamma range (50-200 Hz). Propofol was given i.v. by target-controlled infusion at the lowest concentration required to abolish righting attempts. Physostigmine was given during anaesthesia to produce behavioural arousal without changing anaesthetic concentration. RESULTS: Compared with baseline, gamma/high-gamma power during anaesthesia was reduced by 31% in the cortex (P=0.006) and by 65% in the thalamus (P=0.006). Physostigmine given during anaesthesia increased gamma/high-gamma power in the thalamus by 60% (P=0.048) and caused behavioural arousal that correlated (P=0.0087) with the increase in power. Physostigmine caused no significant power change in the cortex. CONCLUSIONS: We conclude that partial antagonism of propofol anaesthesia by physostigmine is associated with an increase in thalamic activity reflected in gamma/high-gamma (50-200 Hz) power. These findings are consistent with the view that anaesthetic-induced unconsciousness is associated with impairment of thalamic function.

Critical involvement of the thalamus and precuneus during restoration of consciousness with physostigmine in humans during propofol anaesthesia: a positron emission tomography study.

BACKGROUND: Functional brain imaging offers a way to investigate how general anaesthetics impair consciousness. However, functional imaging changes may result from drug effects unrelated to hypnosis. Establishing a causal link with loss of consciousness is thus difficult. METHODS: To identify changes of neuronal activity functionally linked to the level of consciousness, physostigmine was used to restore consciousness without changing the anaesthetic concentration in 11 subjects anaesthetized with propofol. Eight subjects (responders) regained consciousness after physostigmine and three did not (non-responders). Positron emission tomography was used to measure regional cerebral blood flow (rCBF); during baseline (awake), after anaesthesia-induced loss of consciousness, after physostigmine administration, and recovery. In addition to subtraction analyses, we used conjunction analysis in the responders to identify changes common to the baseline-anaesthesia and physostigmine-anaesthesia contrasts. RESULTS: Complete data were available for seven subjects (four responders and three non-responders). The analyses revealed that unconsciousness was associated with rCBF decreases in the thalamus and precuneus. Restoration of consciousness by physostigmine was associated with rCBF increases in these same structures, with the strongest effect in the thalamus. CONCLUSIONS: The results provide strong evidence that reductions in rCBF in the thalamus and precuneus are functionally related to propofol-induced unconsciousness independently of any non-specific effects of propofol. These observations confirm that the thalamus and precuneus are key elements to understand how general anaesthetics cause unconsciousness and how patients wake up from anaesthesia. Furthermore, they are consistent with the notion that anaesthetic-induced unconsciousness is associated with reduced cholinergic activation.

Impact of dietary fat content and fat oxidation on energy intake in humans.

Three studies were performed to assess the effects of a high-fat diet and exercise-induced changes in fat oxidation on energy intake in humans. In the first study the short-term effect of a high-fat diet on spontaneous energy intake was investigated. The second study evaluated the long-term effect of a high-fat diet on adiposity and the third study evaluated the effect of exercise-induced changes in fat oxidation on short-term regulation of energy intake when subjects were consuming a high-fat diet. The results of these studies indicate that a high-fat diet induces a short-term hyperphagia, a high percentage of lipids in the usual diet is associated with a higher adiposity, and exercise may attenuate or amplify the high-fat, diet-induced hyperphagia, depending on the magnitude of the exercise-induced increase in fat oxidation.

Temperature during cardiopulmonary bypass for coronary artery operations does not influence postoperative cognitive function: a prospective, randomized trial.

OBJECTIVE: The objective was to examine the effect of temperature (28 degrees vs 36 degrees C) during cardiopulmonary bypass on postoperative cognitive functions in a prospective, double-blind, and randomized manner. METHODS: Sixty-two patients scheduled for coronary operations were randomized to warm or cold cardiopulmonary bypass. Preoperative and postoperative (7 days) neuropsychologic evaluations were performed by an observer unaware of cardiopulmonary bypass temperature. RESULTS: Fifty-four patients completed the study (cold bypass, n = 24; warm bypass, n = 30). Significant (p < 0.01) postoperative deterioration for tests of psychomotor coordination and verbal memory was noted in both warm and cold groups, but no differences were observed between groups. CONCLUSION: Temperature during cardiopulmonary bypass for coronary operations does not influence postoperative cognitive function.

The role of radiologic methods in assessing body composition and related metabolic parameters.

The measurement of body composition and related metabolic parameters has become an important issue in clinical nutrition. Numerous techniques to assess visceral fat, which is strongly associated with metabolic disorders, have been developed. Other techniques focus mainly on the measurement of specific body components related to metabolic disturbances. This paper reviews methods that directly assess body composition and associated metabolic parameters. The principles of these methods and their accuracy, reproducibility and safety, as well as the clinical implications of their use, are discussed. Recent studies have documented the safety and efficacy of radiologic methods of assessing visceral fat, muscle mass, and morphology to obtain body composition data related to metabolic disturbances. Because these techniques have been documented to be safe and effective, clinicians should consider using them in the evaluation and follow-up of patients with various conditions.

Understanding enediyne-protein interactions: diyl atom transfer results in generation of aminoacyl radicals.

[formula: see text] The origin of the protein modulating capacity of enediynes has been probed. A series of synthetic enediyne-derived diyls participated in atom transfer chemistry with a labeled amino acid. Subsequent experiments suggest that diyl radicals may modulate protein architecture via formation of captodatively stabilized radicals.

Physical training increases beta-adrenoceptor density and adenylate cyclase activity in high-oxidative skeletal muscle of diabetic rats.

The effects of physical training on beta-adrenergic-receptor density (Bmax) and adenylate cyclase (AC) activity in soleus muscles (type I) and the deep red portion (type IIa) and superficial white portion (type IIb) of vastus lateralis muscles in diabetic rats were investigated. Rats were rendered diabetic with streptozotocin ([STZ] 45 mg/kg intravenously [IV]) and were either kept sedentary ([SD] n = 12) or submitted to a progressive 10-week treadmill running program ([TD] n = 13). A group of normal sedentary rats served as controls ([SC] n = 13). Plasma glucose levels were increased in SD rats in comparison with SC rats (21.3 +/- 1.4 mmol/L v 7.7 +/- 0.2; mean +/- SE, P < .001), but levels were partially reversed to normal by training (10.7 +/- 1.7; P < .01 v SD). The gastrocnemius nicotinamide adenine dinucleotide (NAD)-isocitrate dehydrogenase (ICDH) activity was significantly increased in TD rats in comparison to SC or SD rats (P < .001). The Bmax and antagonist affinity (Kd) determined with 125iodocyanopindolol (ICYP) were not affected by diabetes in any of the three types of muscle. In type I muscle, TD rats showed a significant 67% increase in Bmax compared with that of SD rats (TD 26.7 +/- 2.0 v SD 16.0 +/- 1.0; P < .001). In type IIa muscle, Bmax was significantly higher by 68% in TD rats as compared with SD rats (TD 16.5 +/- 1.7 v SD 9.8 +/- 0.9 fmol/mg protein; P < .01).(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of physical training on ventricular beta-adrenergic receptor adenylate cyclase system of diabetic rats.

This study was designed to assess the effect of physical training on the ventricular beta-adrenergic receptor adenylate cyclase system of diabetic rats. Mild diabetes mellitus was induced by an intravenous (IV) injection of streptozotocin (45 mg/kg). Rats were randomized into a group submitted to a progressive 10-week running program on a treadmill, while another group was kept sedentary. A group of sedentary nondiabetic rats was used as normal controls. Results showed a similar reduction in the density of beta-adrenergic receptors in sedentary diabetic (P less than .05) and trained diabetic rats (P less than .01) compared with controls, without any significant alteration in the dissociation constant. The basal and the sodium fluoride-stimulated maximal adenylate cyclase activities were similar in the three groups. However, the maximal response of adenylate cyclase to isoproterenol was significantly reduced in the two diabetic groups compared with controls (P less than .01). The decrease in adenylate cyclase response to isoproterenol observed in the diabetic groups appeared to be associated with a reduction in the total number of beta-adrenergic receptors and more specifically in those existing in the high-affinity state. On the other hand, the hyperglycemia and hyperglucagonemia present in sedentary diabetic rats was improved by training. These data suggest that the beneficial effects observed in response to training in experimental diabetes are not associated with changes in beta-adrenergic receptor adenylate cyclase system on membranes from ventricular tissue.

Effect of endurance training on beta-adrenergic system in three different skeletal muscles.

The beta-adrenergic receptor density (Bmax) and adenylate cyclase (AC) activity in the soleus muscle and deep red and white superficial portions of the vastus lateralis muscle were evaluated in a group of rats submitted to a progressive 10-wk treadmill running program (n = 19) and compared with a group of rats kept sedentary (n = 17) during the same period of time.(ABSTRACT TRUNCATED AT 250 WORDS)

Beta-adrenoceptor adenylate cyclase system adaptation to physical training in rat ventricular tissue.

The beta-adrenergic receptor adenylate cyclase system of ventricular tissue was evaluated in a group of rats submitted to a progressive 10-wk running program on a treadmill and compared with that in a group of rats maintained sedentary during the same period. Adequate training was confirmed by a 46% increase in the gastrocnemius isocitrate dehydrogenase activity in the trained group [1.50 +/- 0.04 vs. 1.03 +/- 0.06 (SE) pmol.g-1.min-1; P less than 0.01). Binding studies with [125I]iodocyanopindolol showed a 13% reduction in the density of beta-adrenergic receptors in trained rats (42.6 +/- 2.1 vs. 49.0 +/- 2.1 fmol/mg; P less than 0.05) without any significant modification in the dissociation constant. The amount of [125I]iodocyanopindolol bound to beta-adrenoceptors in the high-affinity state was reduced by 16.6% in trained rats (12.5 +/- 0.9 vs. 15.0 +/- 0.5 fmol/mg; P less than 0.05) without any significant changes for those in the low-affinity state, indicating a decrease in the coupling between the beta-adrenergic receptors and the guanine stimulatory binding protein. Furthermore, although the basal and sodium fluoride-stimulated adenylate cyclase activities were similar in the two groups of rats, the response of adenylate cyclase maximally stimulated by 10(-5) M isoproterenol was reduced by 16% in trained rats (29.7 +/- 1.4 vs. 35.3 +/- 1.3 pmol.mg-1.min-1; P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

The cardiomyopathy in Friedreich's ataxia: isotopic ventriculography and myocardial imaging with thallium-201.

Myocardial scanning after the intravenous administration of Thallium 201 was used to evaluate regional myocardial perfusion in 14 patients with Friedreich's ataxia. Isotopic ventriculography was also used to assess left ventricular contractility. Myocardial images in patients with Friedreich's ataxia were found to be precociously abnormal irrespective of the degree of neurological impairment or of the severity of myocardial hypertrophy.

Auditory evoked potentials.

This chapter will focus on the two auditory evoked potentials (AEP) most commonly used to assess the effects of general anesthetics on the brain, the auditory middle latency response (AMLR) and the 40 Hz auditory steady-state response (40 Hz-ASSR). We will review their physiological basis, the recording methodology, the effects of general anesthetics, their ability to track changes in level of consciousness and their clinical applications. Because of space constraints, this review will be limited to human studies.

Treating obesity. Lost cause or new opportunity?

OBJECTIVE: To review therapies for treating obese patients. QUALITY OF EVIDENCE: Advice in this paper is based mainly on the results of randomized controlled trials. Some data from smaller, more physiologic studies are included. When appropriate, advice is based on consensus. MAIN MESSAGE: Recent medical evidence indicates that a modest weight loss (5% to 10%) can alleviate symptoms of obesity-related comorbidity. Treatment of obesity should be comprehensive and integrated into a multi-component approach and should involve both patients and their families. The main challenge of obesity is maintaining a reduced weight. CONCLUSION: A multi-component approach to treating obesity can help make treatment less frustrating and more rewarding for patients and physicians.

The effects of propofol on the 40-Hz auditory steady-state response and on the electroencephalogram in humans.

The auditory steady-state response (ASSR) is a nearly sinusoidal electrical response of the brain to auditory stimuli delivered at fast rates. The amplitude of the response is largest for stimulus rates near 40/s, hence the label 40-Hz ASSR. We have studied the effects of propofol (1.5 mg/kg) on the 40-Hz ASSR in 14 patients. The spectral edge frequency (SEF) and median frequency (MDF) of the electroencephalogram were recorded for comparison. The study was limited to 6 min after the injection of propofol. Recordings were obtained every minute. Consciousness, defined as responsiveness to verbal command, was assessed in all patients within 1 min. Nine patients, regained consciousness before the end of the study. Propofol caused disappearance of the 40-Hz ASSR for 2 min. Th 40-Hz ASSR reappeared afterward, reaching, at the end of the study period, an amplitude of about 65% of baseline. Recovery of the 40-Hz ASSR occurred whether or not consciousness was regained during the study, but the amplitude tended to be larger in patients who had regained consciousness compared with patients still unconscious during the same recording. The SEF was reduced by 24% within 2 min and recovered more quickly than the 40-Hz ASSR, reaching 91% of baseline within 4 min. The SEF tended to be higher in patients who had regained consciousness. The MDF was reduced by 27% within 2 min, and exceeded baseline values by 25% during recovery. The MDF was not higher in patients who had regained consciousness. We conclude that propofol transiently abolishes the 40-Hz ASSR. Recovery of the 40-Hz ASSR occurs whether or not consciousness is regained, but the 40-Hz ASSR tends to be larger after the return of consciousness. An association between higher amplitude 40-Hz ASSR and the return of consciousness could not be conclusively established, perhaps because of low signal-to-noise ratio in three patients. The 40-Hz ASSR did not offer any clear advantage over the SEF in predicting the return of consciousness.

Comparison of the effects of enflurane/N2O on the 40-Hz auditory steady-state response versus the auditory middle-latency response.

The auditory middle-latency response (AMLR) is a sequence of negative-positive waves occurring 12-50 ms after the onset of an auditory stimulus presented at rates of 10/s or less. When the rate of stimulus presentation is increased to approximately 40/s, overlapping of the AM-LRs results in a sustained, nearly sinusoidal wave, called the "40-Hz auditory steady-state response" (40-Hz ASSR). The AMLR and 40-Hz ASSR have been used to study the effects of general anesthetics on the brain. The primary aim of this investigation was to determine whether the effects of a general anesthetic, namely enflurane, on the 40-Hz ASSR can be predicted from its effects on the AMLR. A secondary aim was to examine the relationship between the level of consciousness and the 40-Hz ASSR during emergence from anesthesia. Twelve ASA class I-II women undergoing reduction mammoplasty were tested. Anesthesia was induced with fentanyl (3 micrograms/kg) and thiopental (3-5 mg/kg) intravenously and was maintained with enflurane (0.5%, 0.8%, or 1.1% end-tidal; four patients per concentration; random assignment) in N2O (66% end-tidal), along with fentanyl (1 microgram/kg as needed). The 40-Hz ASSR and AMLR were recorded before induction and during anesthesia and surgery. The 40-Hz ASSR was also recorded during emergence. The amplitude of the 40-Hz ASSR was reduced profoundly during anesthesia and surgery (P < 0.001). The attenuation was not dose-dependent, and was much more pronounced than predicted by the effects of enflurane on the AMLR. The 40-Hz ASSR during anesthesia was surprisingly large (0.09 and 0.11 microV) in two patients, both of the 1.1% enflurane group. The regaining of the ability to follow verbal commands was associated with a significant (P < 0.001) increase in the amplitude of the 40-Hz ASSR. We conclude that, although auditory neurons remain capable of responding at a slow stimulus rate during enflurane-N2O anesthesia, their ability to be driven at a faster stimulus rate is markedly curtailed. The 40-Hz ASSR may be useful for detecting unintentional intraoperative awareness because the return of consciousness is associated with a clear increase in amplitude.

Long-latency auditory evoked potentials during general anesthesia: N1 and P3 components.

The N1 and P3 auditory evoked potentials were recorded to evaluate their usefulness as measures of the level of consciousness in 14 ASA physical status I and II patients undergoing elective surgery. The anesthetic agents were thiopental, fentanyl, and isoflurane with or without nitrous oxide. Recordings were carried out before induction (preinduction) and during induction, surgical anesthesia, emergence, and recovery from anesthesia. The auditory response was evoked by 700-Hz tones that occurred occasionally and unpredictably in a train of 500-Hz tones delivered at 40 per second. The patients were asked to press a button whenever they detected a 700-Hz tone. Studies with normal subjects have repeatedly shown that detected tones (HITS) evoke N1 and P3 waves, whereas undetected tones (MISSES) evoke no recognizable waves. The responses evoked by HITS were compared with those evoked by MISSES. The amplitudes of N1 and P3 were significantly different from zero for HITS before induction and during induction and recovery but not during emergence. The amplitudes of N1 and P3 were not different from zero for MISSES during induction, surgery, and emergence. During recovery, the N1 and P3 for MISSES were small and the P3 for HITS was significantly larger than for MISSES. The results indicate that except during emergence, HITS were associated with clear N1 and P3 waves, whereas MISSES were not. The lack of either N1 or P3 for HITS during emergence perhaps occurred because the patients, although responsive, were not yet fully conscious. The N1 and P3 components of the auditory evoked potential may provide specific indicators for consciousness.

The long-latency auditory evoked potential as a measure of the level of consciousness during sufentanil anesthesia.

The long-latency auditory evoked potential was recorded during opioid anesthesia to evaluate its usefulness for assessing the level of consciousness. Eight patients undergoing coronary artery surgery under high-dose sufentanil anesthesia following a lorazepam premedication were tested. Four waves were studied: the N1, P2, P3, and the slow wave (SW). The amplitude of N1 and that of the SW were reduced by sufentanil, but the differences did not reach significance. The amplitude and latency of P2 and the latency of the SW were significantly reduced. The P3, which is possibly a specific indicator for consciousness, was present before induction and absent during anesthesia. There was no conscious recall for intraoperative events. Preservation of the N1, P2, and SW, which are abolished by nonopioid general anesthetics, suggests that auditory processing proceeds further during anesthesia with sufentanil. However, no electrophysiologic evidence of consciousness was found during sufentanil anesthesia.

The auditory steady state response during sufentanil anaesthesia.

The auditory steady state response (ASSR) is a sinusoidal evoked potential elicited by rapidly repeated auditory stimuli. The ASSR was recorded in eight patients during high-dose sufentanil anaesthesia for cardiac surgery in order to assess its usefulness as a measure of the level of consciousness. The electroencephalogram (EEG) was recorded for comparison. The ASSR was present before induction in all patients. It was attenuated severely or possibly abolished with loss of consciousness, and reappeared at low amplitude 5-10 min later and remained attenuated until the end of surgery. The amplitude increased with early signs of awakening in the Intensive Care Unit. With few exceptions, changes in the simultaneously recorded EEG were similar to those of the ASSR. The ASSR deserves further evaluation as a tool for monitoring level of consciousness during high-dose opioid anaesthesia.